Drug Nanocarriers Labeled With Near-infrared-emitting Quantum Dots (Quantoplexes): Imaging Fast Dynamics of Distribution in Living Animals

Abstract

The knowledge of the biodistribution of macromolecular drug formulations is a key to their successful development for specific tissue- and tumor-targeting after systemic application. Based on the polyplex formulations, we introduce novel drug nanocarriers, which we denote as "quantoplexes" incorporating near-infrared (IR)-emitting cadmium telluride (CdTe) quantum dots (QDs), polyethylenimine (PEI), and a macromolecular model drug [plasmid DNA (pDNA)], and demonstrate the ability of tracking these bioactive compounds in living animals. Intravenous application of bare QD into nude mice leads to rapid accumulation in the liver and peripheral regions resembling lymph nodes, followed by clearance via the liver within hours to days. Quantoplexes rapidly accumulate in the lung, liver, and spleen and the fluorescent signal is detectable for at least a week. Tracking quantoplexes immediately after intravenous injection shows rapid redistribution from the lung to the liver within 5 minutes, depending on the PEI topology and quantoplex formulation used. With polyethyleneglycol (PEG)-modified quantoplexes, blood circulation and passive tumor accumulation was measured in real time. The use of quantoplexes will strongly accelerate the development of tissue and tumor-targeted macromolecular drug carriers.

Multi-spectroscopic techniques to evaluate the toxicity of alloyed CdSeS quantum dots

“…These advantageous features of QDs have endowed them as promising optical probes in biomedicine and biotechnology [2]. Therefore, investigation of QDs' biological toxicity becomes a must before their extensive application [3][4][5][6][7].…”

Quantum dots–DNA bioconjugates: synthesis to applications

“…This DHLA-PEG hybrid layer has moderate cationic nature along with antifouling properties and can be used to quantitatively load DNA mediated by electrostatic interactions [65]. Other strategy involves using small molecule ligands such as MPA (negative charge) followed by PEI (polyethylenimine) [66][67][68]. These high to moderately cationic QDs have been extensively used to electrostatically assemble excess of DNA for biodetection and delivery of therapeutically active agents.…”

MicroRNA and Drug Delivery

“…Further, their accumulation in RES organs such as the lung, liver, and spleen makes them difficult to target elsewhere. Because of their recognition by the host as foreign, antibodies are made and further dosing results in more decreased delivery as well as stimulating the body to reject any cells transduced by the foreign viral particles [290][291][292][293].…”